Influence of Gut Microbial Communities on Fasting and Postprandial Lipids and Circulating Metabolites: The PREDICT 1 Study

Abstract Objectives The human gut microbiome plays a critical role in host glucose metabolism, but its connections to other key markers of cardiometabolic health in fasting and postprandial conditions is largely unknown. The PREDICT 1 study enrolled n = 1,102 twins and unrelated healthy US/UK adults to explore the genetic, metabolic, microbial, and meal determinants of fasting metabolites and postprandial responses to foods. Methods This multi-centre dietary study assessed fasting and postprandial (0-6h) circulating metabolites over a 13d study period incorporating standardized test meals of varying nutrient composition. Shotgun metagenomics was performed from samples collected at baseline (n = 1,001 UK and 97 US). Metabolomics (NMR) was performed on clinic fasting and postprandial samples, blood glucose was continuously assessed, and blood triglycerides and C-peptide were serially measured. Results Using machine learning models, we found the fasting metabolites most strongly associated with overall gut community structure were the inflammatory marker GlycA (r = 0.31), and HDL and VLDL particle diameter (HDL-D and VLDL-D; r = 0.3 and 0.28 respectively). Variance explained was slightly greater for postprandial HDL-D and VLDL-D (at 6h; r = 0.32 and 0.31, respectively) than fasting levels, whilst the other metabolites did not differ (e.g., GlycA r = 0.28). Lipid-mediated metabolites were more closely associated with the gut microbiome in both fasting and postprandial states compared with glycemic-mediated measurements. There were distinct microbial clusters that segregated both fasting and postprandial metabolites according to their known association with cardiometabolic disease; ApoA and HDL vs. ApoB, VLDL, IDL LDL, remnant C, GlycA, IL-6, blood pressure, glucose, insulin and HbA1c. We also identified differential abundance among several microbes associated with metabolic health, including Prevotella copri and Faecalibacterium prausnitzii. Results obtained in the UK cohort were validated in the US cohort. Conclusions An individual's gut microbial composition is predictive of their cardiometabolic markers and personalized responses to food. Our data highlight the potential of the gut microbiome as a target amenable to modulation in personalized nutrition to ameliorate cardiometabolic risk. Funding Sources Zoe Global Ltd., NIHR GSTT BRC, Wellcome Trust.

Download Full-text

Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

The ISME Journal ◽

10.1038/s41396-021-00998-8 ◽

2021 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Gut Microbiome ◽

Human Gut ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

Download Full-text

The Gut Microbiome and Xenobiotics: Identifying Knowledge Gaps

Toxicological Sciences ◽

10.1093/toxsci/kfaa060 ◽

2020 ◽

Vol 176 (1) ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Vicki L Sutherland ◽

Charlene A McQueen ◽

Donna Mendrick ◽

Donna Gulezian ◽

Carl Cerniglia ◽

...

Keyword(s):

Human Health ◽

Gut Microbiome ◽

Critical Role ◽

Drug Efficacy ◽

Model Systems ◽

Microbial Composition ◽

Breakout Group ◽

Data Gaps ◽

Critical Issues ◽

And Function

Abstract There is an increasing awareness that the gut microbiome plays a critical role in human health and disease, but mechanistic insights are often lacking. In June 2018, the Health and Environmental Sciences Institute (HESI) held a workshop, “The Gut Microbiome: Markers of Human Health, Drug Efficacy and Xenobiotic Toxicity” (https://hesiglobal.org/event/the-gut-microbiome-workshop) to identify data gaps in determining how gut microbiome alterations may affect human health. Speakers and stakeholders from academia, government, and industry addressed multiple topics including the current science on the gut microbiome, endogenous and exogenous metabolites, biomarkers, and model systems. The workshop presentations and breakout group discussions formed the basis for identifying data gaps and research needs. Two critical issues that emerged were defining the microbial composition and function related to health and developing standards for models, methods and analysis in order to increase the ability to compare and replicate studies. A series of key recommendations were formulated to focus efforts to further understand host-microbiome interactions and the consequences of exposure to xenobiotics as well as identifying biomarkers of microbiome-associated disease and toxicity.

Download Full-text

Distinct gut microbial communities and metabolic functions are associated with cachexia in lung cancer patients

10.21203/rs.3.rs-30539/v1 ◽

2020 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Clinical Setting ◽

Gut Microbiome ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

Abstract Background Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in the clinical setting by integrating shotgun metagenomics and plasma metabolomics of 38 lung cancer patients, with known cachexia status. Results The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, as well as vitamins, were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of plasma BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with the gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in the cancer cachectic patients. The involvement of gut microbiome in cachexia was further observed in a high-performance machine learning model that uses solely gut microbial taxonomic and pathway features to differentiate cachectic from non-cachectic cancer patients. Conclusions Our study demonstrates the links between host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible future therapeutic applications.

Download Full-text

Cross-Sectional Study on the Gut Microbiome of Parkinson’s Disease Patients in Central China

Frontiers in Microbiology ◽

10.3389/fmicb.2021.728479 ◽

2021 ◽

Vol 12 ◽

Author(s):

Liangwei Mao ◽

Yu Zhang ◽

Jing Tian ◽

Ming Sang ◽

Guimin Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiome ◽

Clinical Symptoms ◽

Characteristic Curve ◽

Central China ◽

Metagenomic Sequencing ◽

Microbial Composition ◽

Protein Database ◽

Shotgun Metagenomics

Gastrointestinal dysfunction plays an important role in the occurrence and development of Parkinson’s disease (PD). This study investigates the composition of the gut microbiome using shotgun metagenomic sequencing in PD patients in central China. Fecal samples from 39 PD patients (PD group) and the corresponding 39 healthy spouses of the patients (SP) were collected for shotgun metagenomics sequencing. Results showed a significantly altered microbial composition in the PD patients. Bilophila wadsworthia enrichment was found in the gut microbiome of PD patients, which has not been reported in previous studies. The random forest (RF) model, which identifies differences in microbiomes, reliably discriminated patients with PD from controls; the area under the receiver operating characteristic curve was 0.803. Further analysis of the microbiome and clinical symptoms showed that Klebsiella and Parasutterella were positively correlated with the duration and severity of PD, whereas hydrogen-generating Prevotella was negatively correlated with disease severity. The Cluster of Orthologous Groups of protein database, the KEGG Orthology database, and the carbohydrate-active enzymes of gene-category analysis showed that branched-chain amino acid–related proteins were significantly increased, and GH43 was significantly reduced in the PD group. Functional analysis of the metagenome confirmed differences in microbiome metabolism in the PD group related to short-chain fatty acid precursor metabolism.

Download Full-text

Exploring changes in the human gut microbiota and microbial-derived metabolites in response to diets enriched in simple, refined, or unrefined carbohydrate-containing foods: a post hoc analysis of a randomized clinical trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa254 ◽

2020 ◽

Vol 112 (6) ◽

pp. 1631-1641

Author(s):

Tyler Faits ◽

Maura E Walker ◽

Jose Rodriguez-Morato ◽

Huicui Meng ◽

Julie E Gervis ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Cardiometabolic Risk ◽

Cardiometabolic Health ◽

Microbial Composition ◽

Carbohydrate Diet ◽

Secondary Bile Acid ◽

Stress Genes ◽

Post Hoc ◽

Simple Carbohydrate

ABSTRACT Background Dietary carbohydrate type may influence cardiometabolic risk through alterations in the gut microbiome and microbial-derived metabolites, but evidence is limited. Objectives We explored the relative effects of an isocaloric exchange of dietary simple, refined, and unrefined carbohydrate on gut microbiota composition/function, and selected microbial metabolite concentrations. Methods Participants [n = 11; age: 65 ± 8 y; BMI (in kg/m2): 29.8 ± 3.2] were provided with each of 3 diets for 4.5 wk with 2-wk washout, according to a randomized, crossover design. Diets [60% of energy (%E) carbohydrate, 15%E protein, and 25%E fat] differed in type of carbohydrate. Fecal microbial composition, metatranscriptomics, and microbial-derived SCFA and secondary bile acid (SBA) concentrations were assessed at the end of each phase and associated with cardiometabolic risk factors (CMRFs). Results Roseburia abundance was higher (11% compared with 5%) and fecal SBA concentrations were lower (lithocolic acid –50% and deoxycholic acid –64%) after consumption of the unrefined carbohydrate diet relative to the simple carbohydrate diet [false discovery rate (FDR): all P < 0.05), whereas Anaerostipes abundance was higher (0.35% compared with 0.12%; FDR: P = 0.04) after the simple carbohydrate diet relative to the refined carbohydrate diet. Metatranscriptomics indicated upregulation of 2 cellular stress genes (FDR: P < 0.1) after the unrefined carbohydrate diet compared with the simple carbohydrate or refined carbohydrate diets. The microbial expression of 3 cellular/oxidative stress and immune response genes was higher (FDR: P < 0.1) after the simple carbohydrate diet relative to the refined carbohydrate diet. No significant diet effect was observed in fecal SCFA concentrations. Independent of diet, we observed 16 associations (all FDR: P < 0.1) of taxon abundance (15 phylum and 1 genera) with serum inflammatory markers and also with fecal SCFA and SBA concentrations. Conclusions Consuming an unrefined carbohydrate–rich diet had a modest effect on the gut microbiome and SBAs, resulting in favorable associations with selected CMRFs. Simple carbohydrate– and refined carbohydrate–rich diets have distinctive effects on the gut microbiome, suggesting differential mechanisms mediate their effects on cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT01610661.

Download Full-text

The Impact of Microbial Composition on Postprandial Glycaemia and Lipidaemia: A Systematic Review of Current Evidence

Nutrients ◽

10.3390/nu13113887 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3887

Author(s):

Megan L. Wilson ◽

Ian G. Davies ◽

Weronika Waraksa ◽

Sayyed S. Khayyatzadeh ◽

Maha Al-Asmakh ◽

...

Keyword(s):

Gut Microbiome ◽

Health Management ◽

Current Evidence ◽

Cardiometabolic Health ◽

Cochrane Central Register ◽

Microbial Composition ◽

Current Review ◽

Microbiome Diversity ◽

Increased Risk ◽

The Impact

Postprandial hyperglycaemia is associated with increased risk of cardiovascular disease. Recent studies highlight the role of the gut microbiome in influencing postprandial glycaemic (PPG) and lipidaemic (PPL) responses. The authors of this review sought to address the question: “To what extent does individual gut microbiome diversity and composition contribute to PPG and PPL responses?” CINAHL Plus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from January 2010 to June 2020. Following screening, 22 studies were eligible to be included in the current review. All trials reported analysis of gut microbiome diversity and composition and PPG and/or PPL. Results were reported according to the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analysis’ (PRISMA) statement. Individual microbiota structure was found to play a key role in determining postprandial metabolic responses in adults and is attributed to a complex interplay of diet, microbiota composition, and metagenomic activity, which may be predicted by metagenomic analysis. Alterations of gut microbiota, namely relative abundance of bacterial phylum Actinobacteria and Proteobacteria, along with Enterobacteriaceae, were associated with individual variation in postprandial glycaemic response in adults. The findings of the current review present new evidence to support a personalised approach to nutritional recommendations and guidance for optimal health, management, and treatment of common metabolic disorders. In conclusion, personalised nutrition approaches based on individual microbial composition may improve postprandial regulation of glucose and lipids, providing a potential strategy to ameliorate cardiometabolic health outcomes.

Download Full-text

Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽

10.3390/life11030246 ◽

2021 ◽

Vol 11 (3) ◽

pp. 246

Author(s):

Felix C.F. Schmitt ◽

Martin Schneider ◽

William Mathejczyk ◽

Markus A. Weigand ◽

Jane C. Figueiredo ◽

...

Keyword(s):

Colorectal Cancer ◽

Postoperative Complications ◽

Gut Microbiota ◽

Gut Microbiome ◽

Tumor Resection ◽

Microbial Composition ◽

Colorectal Cancer Surgery ◽

Long Term Changes ◽

Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

Download Full-text

Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota

Microbiome ◽

10.1186/s40168-021-01029-6 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Shasha Xiang ◽

Kun Ye ◽

Mian Li ◽

Jian Ying ◽

Huanhuan Wang ◽

...

Keyword(s):

Gut Microbiome ◽

Lactobacillus Reuteri ◽

Carbon Sources ◽

Short Chain Fatty Acids ◽

Microbial Composition ◽

Key Enzymes ◽

Rrna Sequencing ◽

Phosphate Acetyltransferase

Abstract Background Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts. Results In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate. Conclusions Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs.

Download Full-text

Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome

European Heart Journal ◽

10.1093/ehjci/ehaa946.3823 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Roessler ◽

F Zimmermann ◽

D Schmidt ◽

U Escher ◽

A Jasina ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

Interindividual Variation ◽

Funding Source ◽

Microbial Composition ◽

Atorvastatin Treatment ◽

Qrt Pcr ◽

16S Rna ◽

Regulatory Properties

Abstract Background and aims The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome. Methods Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR. Results In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment. Conclusions Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation

Download Full-text

A Mixed-Methods Investigation into Barriers for Sharing Geospatial and Resilience Flood Data in the UK

Water ◽

10.3390/w13091235 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1235

Author(s):

Luke Waterman ◽

Mónica Rivas Casado ◽

Emma Bergin ◽

Gary McInally

Keyword(s):

Data Sharing ◽

Local Politics ◽

Critical Role ◽

Third Sector ◽

Structured Interviews ◽

Average Temperature ◽

Third Sector Organisations ◽

Data Points ◽

The Uk

With increases in average temperature and rainfall predicted, more households are expected to be at risk of flooding in the UK by 2050. Data and technologies are increasingly playing a critical role across public-, private- and third-sector organisations. However, barriers and constraints exist across organisations and industries that limit the sharing of data. We examine the international context for data sharing and variations between data-rich and data-sparse countries. We find that local politics and organisational structures influence data sharing. We focus on the case study of the UK, and on geospatial and flood resilience data in particular. We use a series of semi-structured interviews to evaluate data sharing limitations, with particular reference to geospatial and flood resilience data. We identify barriers and constraints when sharing data between organisations. We find technological, security, privacy, cultural and commercial barriers across different use cases and data points. Finally, we provide three long-term recommendations to improve the overall accessibility to flood data and enhance outcomes for organisations and communities.

Download Full-text